Adhesion molecules involved in transendothelial migration of human hematopoietic progenitor cells

In the process of homing, CD34(+) hematopoietic progenitor cells migrate ac ross the bone marrow endothelium in response to stromal cell-derived factor (SDF)-1. To develop more efficient stem cell transplantation procedures, i t is important to define the adhesion molecules involved in the homing proc ess. Here, we identified the adhesion molecules that control the migration of primary human CD34(+) cells across human bone marrow endothelial cells, Migration of CD34(+) cells is enhanced across interleukin Ip prestimulated bone marrow endothelium, suggesting an important role for the endothelium i n adhesion and formation of the chemotactic gradient, Under these condition s, 30-100 ng/ml SDF-1 induced a rapid and efficient migration of CD34(+) ce lls (+/- 46% migration in 3 h), In contrast, 600-1,000 ng/ml SDF-1 mere req uired for optimal migration across fibronectin-coated filters. Subsequent s tudies revealed that transendothelial migration of CD34(+) cells is mediate d by beta1- and beta2-integrins and PECAM-1 (CD31) but not by CD34 or E-sel ectin, Whereas these antibodies individually blocked migration for 25%-35%, migration was reduced by 68% when the antibodies were combined. Thus, thes e adhesion molecules play specific and independent roles in the transmigrat ion process. Finally, O-glycosylated proteins appeared to play a role, sinc e SDF-1-induced migration of CD34(+) cells (treated with a glycoprotease fr om Pasteurella haemolytica) across endothelial cells was clearly inhibited. In conclusion, we show that efficient SDF-1-induced migration of primary hu man CD34(+) cells across bone marrow endothelium is mediated by beta1-integ rins, beta2-integrins, CD31 and O-glycosylated proteins.